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Biomedical subjects

G Ambrosini

Publications and source records attributed to G Ambrosini.

At least 37 records · Page 2Linked to original sources
PubMed2001

Placental and fetal pulsatility indices in gestational diabetes mellitus.

OBJECTIVE: To assess the usefulness of placental and fetal Doppler velocimetry in the surveillance of gestational diabetes mellitus (GDM). STUDY DESIGN: We studied 89 patients with GDM. All fetuses underwent umbilical, fetal descending thoracic aorta and fetal middle cerebral artery pulsatility index (PI) assessment. Doppler results were not used for management. We correlated PI with route of delivery and with the following perinatal complications: small size for gestational age, cesarean section (CS) for acute fetal distress (AFD), respiratory distress syndrome, hyperbilirubinemia, hypocalcemia, hypoglycemia, macrosomia and stay in a neonatal intensive care unit. RESULTS: Seventy-seven patients (87%) had normal Doppler measurements, while 12 (13%) showed one or more abnormal measurements. The greatest incidence of CS for AFD (42% vs. 16%, P < .001), as well as neonatal hyperbilirubinemia (25% vs. 10%, P < .001) and hypoglycemia (25% vs. 5%, P < .001) was reported among the women with abnormal Doppler measurements. CONCLUSION: Fetal placental hemodynamics are normal in most cases of GDM. In a small percentage of cases we observed abnormal fetal placental PI associated with a higher incidence of perinatal complications. Hence, the finding of abnormal PI must induce the physician to carry out more intensive obstetric care of women with GDM.

Adult↗
PubMed2001

Immunohistochemical evaluation of a new epithelial antigen, Ber-EP4, in ovarian cancer: preliminary results.

OBJECTIVE: To assess the immunohistochemical expression of Ber-EP4, a new epithelial antigen in ovarian cancer. METHODS: We studied 25 cases of ovarian cancer in which Ber-EP4, CEA and CA 125 were investigated by an immunohistochemical method. We evaluated the correlations between immunohistochemical positivity and grading, histotype and stage of disease. RESULTS: CEA was positive in 5 out of 25 cases (20%), CA-125 in 17 out of 25 cases (68%) and Ber-EP4 in 14 out of 25 cases (56%). Ber-EP4 was mainly present in mucinous tumors in comparison to serous tumors (78.6% vs. 50%). Ber-EP4, as well as CA-125, were directly proportional to tumor differentation (70% of positivity in G1 vs 37.5% in G3 for the former and 80% in G1 vs 50% in G3 for the latter, respectively), whereas CEA showed no relevant difference regarding the grading. There were no differences among the three antigens studied with regard to clinical stage. CONCLUSIONS: In our study Ber-EP4 was positive in 14 out of 22 cases (63.6%) of the primary epithelial ovarian cancers studied. The presence of this antigen seems to be related to histotype and grading but not to clinical stage.

Adult↗
PubMed2001

Prognostic value of p53, c-erb-B2 and MIB-1 in endometrial carcinoma.

OBJECTIVE: To assess the immunohistochemical expression of p53 protein, a tumour suppressor gene of the oncogene c-erb-B2 and MIB-1 proliferation marker (Ki-67 antigen) in endometrial carcinoma. METHODS: We studied 29 cases of endometrial carcinoma in which the p53, c-erb-B2 and MIB-1/Ki-67 antigens were investigated by an immunohistochemical method. We evaluated the correlations among the immunohistochemical positivity and the grading, depth of myometrial invasion, stage of the neoplasia and follow-up. RESULTS: Both p53 and c-erb-B2 were positive in 16 out of 29 cases (55.2%), whereas MIB-1 was positive in 19 out of 29 cases (65.5%). All these three antigens showed a positive correlation with the grading, myometrial invasion and FIGO stage. Regarding follow-up, p53, c-erb-B2 and MIB-1 were, respectively, positive in 100%, 83.4% and 66.7% of neoplasias of patients who died of disease whereas they were positive in 40%, 40% and 60%, respectively, of tumours of patients with no evidence of disease. CONCLUSION: The overexpression of p53, c-erb-B2 and MIB-1 seem to indicate a more malignant tumour phenotype.

Antigens, Nuclear↗
PubMed2000

A second hysterosalpingography reduces the use of selective technique for treatment of a proximal tubal obstruction.

OBJECTIVE: To assess whether a second hysterosalpingography (HSG) can permit tubal patency, reducing the use of selective salpingography in patients with proximal tubal obstruction. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): The study population consisted of 360 infertile women. INTERVENTION(S): In patients with unilateral or bilateral proximal tubal obstruction, a second HSG was performed after about 1 month. In those cases with persistent obstruction, an immediate selective salpingography and tubal catheterization were performed. MAIN OUTCOME MEASURE(S): Tubal opacification. RESULT(S): Forty patients underwent a second HSG procedure for proximal tubal occlusion. Among these, 24 achieved bilateral tubal patency. Thus, repetition of a conventional HSG after 1 month avoided unnecessary salpingography in 60% of patients. CONCLUSION(S): In infertile women with proximal tubal obstruction, we believe it is best to perform a second HSG. HSG is easy to carry out and subjects patients to a lower dosage of radiation and fewer risks than selective salpingography. The latter technique should be reserved for unsuccessful cases.

Adult↗
PubMed2000

Concurrent adjuvant chemotherapy and immediate breast reconstruction with skin expanders after mastectomy for breast cancer.

BACKGROUND: Immediate breast reconstruction (IBR) by means of skin expander is currently one of the most widely used methods of breast reconstruction in mastectomized patients. However, given that many breast cancer patients usually receive adjuvant chemotherapy, the adoption of IBR raises new questions concerning possible cumulative toxicity. The present study reports our experience in the use of concurrent adjuvant chemotherapy and immediate breast reconstruction with skin expander after mastectomy for breast cancer and the acute cumulative toxicity of the treatments. METHODS: We evaluated a consecutive series of 52 breast cancer patients who have received IBR by skin expander after radical mastectomy and adjuvant chemotherapy concurrently during skin expansion between 1995 and 1998 (IBR/CT group). We identified two series of control patients treated during the same period: 51 consecutive patients undergoing radical mastectomy and IBR without adjuvant chemotherapy (IBR group) and 63 consecutive patients undergoing radical mastectomy and adjuvant chemotherapy without IBR (CT group). For each patient, we evaluated the incidence of surgical complications and chemotherapy's side effects and dose intensity. RESULTS: The interval between surgery and the start of expander inflation was similar in IBR/CT (range 0-19, median 5 days) and IBR groups (range 0-40, median 5 days) and the timing of inflation was not influenced by chemotherapy. The overall incidence of surgical complications in patients undergoing IBR was low: seroma in eight cases, infection in one, skin necrosis in one, expander rupture in two and erythema in three. There were no statistically significant differences in the distribution of complications between the IBR/CT and IBR groups. The dose intensity of chemotherapy was similar between IBR/CT and CT groups, with a median dose intensity of 96% and 95% of the projected dose, respectively. The only statistically significant difference in terms of chemotherapy side effects (p = 0.03) was that stomatitis was more frequent and intense in the CT than in the IBR/CT group. CONCLUSIONS: Concurrent treatment with IBR and adjuvant chemotherapy appears feasible and safe, it does not increase acute surgical complications or chemotherapy side effects, and does not require any changes in dose intensity or the timing of inflation.

Adult↗
PubMed2000

Placental corticotropin-releasing factor. An update.

Corticotropin-releasing factor (CRF) produced in placenta has paracrine effects within placenta, decidua, and myometrium and endocrine effects on mother and fetus. CRF is a potent local regulator of myometrial contractility and of prostaglandin release, Recently, urocortin, a new member of the CRF family, has been localized in human placenta and membranes. Urocortin mimics some of the local effects of CRF in intrauterine tissues, that is, increase of adrenocorticotrophic hormone (ACTH) and prostagiandin release and myometrial contractility. A local CRF-BP modulates the paracrine effects of CRF and urocortin. The various CRF receptor subtypes are well distributed in placenta and membranes. CRH also acts on placental blood vasculature and has an action on fetal adrenal gland to stimulate the production of the steroid DHEA-S. In nonpregnant women, plasma CRF levels are low; they become higher during the first and second trimesters of pregnancy. A clear increase is evident at term and when CRF-BP levels decrease. Women with preterm labor show high CRF and low CRF-BP levels, supporting an involvement of this pathway in mechanism of parturition.

Corticotropin-Releasing Hormone↗
PubMed1999

Lactose absorption in patients with ovarian cancer.

To determine whether lactase persistence might be related to ovarian cancer risk, in 1994-1995 the authors assessed the capacity to digest lactose by measuring breath hydrogen production after oral administration of lactose in 50 women with ovarian cancer and 100 healthy controls. All of the women came from Sassari (Sardinia), Italy, an area where the population has a high frequency of lactose malabsorption. Thirty percent of cases were lactose absorbers, as compared with 15% of controls. The odds ratio for ovarian cancer among lactose absorbers was 2.51 (95% confidence interval 1.10-5.68). These results provide some support for a role of lactose ingestion and galactose cytotoxicity in the pathogenesis of ovarian cancer.

Administration, Oral↗
PubMed1999

The value of serum CA 125 and association CA 125/CA 19-9 in endometrial carcinoma.

One hundred and twelve women with endometrial carcinoma were studied with serum sampling to determine preoperative and postoperative levels of CEA, CA 15-3, CA 19-9, TPA and CA 125. After surgical treatment 88 patients had stage I, 8 stage II, 14 stage III and 2 stage IV disease. Before treatment the sensitivity of CEA, CA 15-3, CA 19-9, TPA and CA 125 was 22.3% (25/112), 32.1% (36/112), 22.3% (25/112), 45.5% (51/112), 33.9% (38/112), respectively. According to pathological stage a statistically significant difference between intrauterine (96 cases) and extrauterine disease (16 cases) was noted only for CA 125 (28.1% vs. 68.7%) and CA 15.3 (28.1% vs. 56.2%). In relation to histological grading CA 125 rises progressively from well-differentiated cases to poorly-differentiated tumors. During the follow-up the most reliable marker was CA 125: values more than 35 U/ml of this marker resulted positive in 50% of relapsed cases and only in 5.1% of disease-free cases, thus demonstrating a high specificity. The association of various markers during the follow-up allowed us to reveal interesting results only for the CA 125/CA 19-9 combination. In fact the combined use of these markers permitted a high sensitivity (83.3%), with only 12.8% false positive cases, so with a high specificity.

Adenocarcinoma↗
PubMed1998

Control of apoptosis and mitotic spindle checkpoint by survivin.

Progression of the cell cycle and control of apoptosis (programmed cell death) are thought to be intimately linked processes, acting to preserve homeostasis and developmental morphogenesis. Although proteins that regulate apoptosis have been implicated in restraining cell-cycle entry and controlling ploidy (chromosome number), the effector molecules at the interface between cell proliferation and cell survival have remained elusive. Here we show that a new inhibitor of apoptosis (IAP) protein, survivin, is expressed in the G2/M phase of the cell cycle in a cycle-regulated manner. At the beginning of mitosis, survivin associates with microtubules of the mitotic spindle in a specific and saturable reaction that is regulated by microtubule dynamics. Disruption of survivin-microtubule interactions results in loss of survivin's anti-apoptosis function and increased caspase-3 activity, a mechanism involved in cell death, during mitosis. These results indicate that survivin may counteract a default induction of apoptosis in G2/M phase. The overexpression of survivin in cancer may overcome this apoptotic checkpoint and favour aberrant progression of transformed cells through mitosis.

3T3 Cells↗
PubMed1998

Molecular identification of the cross-reacting epitope on alphaM beta2 integrin I domain recognized by anti-alphaIIb beta3 monoclonal antibody 7E3 and its involvement in leukocyte adherence.

The monoclonal antibody (mAb) 7E3 directed to the platelet integrin alphaIIb beta3 was tested for its cross-reactivity with the homologous leukocyte integrin alphaM beta2. Nested recombinant fragments of alphaM I domain were expressed as glutathione S-transferase fusion proteins and analyzed for antibody recognition. In enzyme-linked immunosorbent assay, mAb 7E3 bound alphaM I domain fragments containing the amino-terminal sequence Cys128-Ser172, whereas the carboxyl-terminal region Leu173-Pro291 was ineffective. A synthetic peptide designated R1.1 and duplicating the alphaM sequence G127CPQEDSDIAFLIDGSGSIIPHDF150 bound mAb 7E3. In contrast, the adjacent alphaM region F150RRMKEFVSTVMEQLKKSKTLFS172 or a control peptide with a scrambled R1.1 sequence was not recognized by mAb 7E3. Binding of mAb 7E3 to alphaM I domain blocked monocyte and neutrophil adhesion to immobilized fibrinogen and fibrinogen-dependent leukocyte-endothelium bridging, indistinguishably from bona fide anti-beta2 mAb IB4. In contrast, leukocyte binding to stable transfectants expressing intercellular adhesion molecule-1 was not affected by mAb 7E3. Balloon-mediated injury of iliofemoral arteries in rabbits resulted in prominent deposition of fibrinogen and increased monocyte adhesion to the injured vessel, in a reaction inhibited by mAb 7E3, but unaffected by control mAb 14E11. Through its cross-reactivity between alphaIIb beta3 and alphaM beta2, mAb 7E3 may initiate a new class of integrin antagonists, capable of simultaneously targeting platelet and leukocyte adhesion mechanisms in vascular injury.

Amino Acid Sequence↗
PubMed1998

Induction of apoptosis and inhibition of cell proliferation by survivin gene targeting.

Survivin is a new IAP apoptosis inhibitor expressed during development and in human cancer in vivo. The coding strand of the survivin gene was extensively complementary to that of effector cell protease receptor-1 (EPR-1), prompting the present investigation on the origin and functional relationship of these two transcripts. Southern blots of genomic DNA were consistent with the presence of multiple, evolutionarily conserved, EPR-1/Survivin-related genes. By pulsed field gel electrophoresis and single- and two-color fluorescence in situ hybridization, these were contained within a contiguous physical interval of 75-130 kilobases (kb) on chromosome 17q25. In Northern blots, a single strand-specific probe identified a 1.3-kb EPR-1 mRNA broadly distributed in normal adult and fetal tissues, structurally distinct from the 1.9-kb Survivin transcript expressed in transformed cell lines. Transient co-transfection of an EPR-1 cDNA potentially acting as a Survivin antisense with a lacZ reporter plasmid resulted in loss of viability of HeLa cells. In contrast, co-transfection of an antisense cDNA of intercellular adhesion molecule-1 or a sense-oriented Survivin cDNA was without effect. In stably transfected HeLa cells, ZnSO4 induction of an EPR-1 mRNA under the control of a metallothionein promoter suppressed the expression of endogenous survivin. This resulted in (i) increased apoptosis as detected by analysis of DNA content and in situ internucleosomal DNA fragmentation and (ii) inhibition of cell proliferation as compared with induced vector control transfectants. These findings suggest the existence of a potential EPR-1/survivin gene cluster and identify survivin as a new target for disrupting cell viability pathways in cancer.

Apoptosis↗
PubMed1998

Multicenter randomized clinical trial on high-dose epirubicin plus cis-platinum versus vinorelbine plus cis-platinum in advanced non small cell lung cancer.

BACKGROUND: High dose Epirubicin (HD-EPI) (>90 mg/m2) and Vinorelbine (VNR) demonstrated antitumor activity as single agent (about 20%) in the treatment of advanced NSCLC. This trial compares these two agents combined with cisplatin (CP). PATIENTS AND METHODS: From August 1992 to February 1996, 228 patients with locally advanced or metastatic NSCLC were randomized to receive either EPI 120 mg/m2 as i.v. bolus plus Cisplatin (CP) 60 mg/m2 on day 1 (regimen A) or VNR 25 mg/m2 as i.v. bolus on day 1 and 8 plus CP 60 mg/m2 on day 1 (regimen B). Both treatments were recycled every 21 days up to a maximum cumulative dose of EPI of 840 mg/m2 or 12 cycles. Eligible patients were 212 and 198 patients were evaluable for objective response (95 in arm A and 103 in arm B). The main characteristics of eligible patients were: male/female 179/33; median age 61 (42-72); median Karnofsky PS 80 (70-100); stage IIIA 12%, stage IIIB 40%, stage IV 41%, recurrence 7%; histotype: epidermoid 48%, adenoca 36%, others 16%. RESULTS: The following response rates were observed in regimens A and B, respectively; CR, 1 and 2%, PR, 32 and 25% (P = 0.4567). Median CR + PR duration was 9 and 8 months, respectively. Median survival was 10.5 and 9.6 months, respectively. Grade III-IV leucopenia occurred in 38 and 21% in arm A and arm B, respectively(P = 0.01), thrombocytopenia in 6 and 0% (P = 0.02), anemia in 8 and 7% (n.s.). Non-hematological toxicity was moderate and the only difference between the treatments was alopecia (88 vs. 33% in arm A and B, respectively). Supraventricular arrhythmia occurred in three patients on regimen A; a >15% LVEF absolute decrease was observed in 9 (22.5%) and three (14%) patients on arm A and arm B, respectively (n.s.). No congestive heart failure was observed. CONCLUSION: HD-EPI+CP and VNR+CP are both active combinations in advanced NSCLC with a similar response rate, response duration and survival but regimen A was significantly more toxic (myelosuppression and alopecia).

Adult↗
PubMed1997

Factor Xa as an interface between coagulation and inflammation. Molecular mimicry of factor Xa association with effector cell protease receptor-1 induces acute inflammation in vivo.

Coagulation proteases were tested in a rat model of acute inflammation. Subplantar injection of Factor Xa (10-30 microg) produced a time- and dose-dependent edema in the rat paw, and potentiated carrageenin-induced edema. In contrast, the homologous protease Factor IXa was ineffective. This inflammatory response was recapitulated by the Factor Xa sequence L83FTRKL88(G), which mediates ligand binding to effector cell protease receptor-1 (EPR-1), while a control scrambled peptide did not induce edema in vivo. Conversely, injection of the EPR-1-derived peptide S123PGKPGNQNSKNEPP137 (corresponding to the receptor binding site for Factor Xa) inhibited carrageenin-induced rat paw edema, while the adjacent EPR-1 sequence P136PKKRERERSSHCYP150 was without effect. EPR-1-Factor Xa-induced inflammation was characterized by fast onset and prominent perivascular accumulation of activated and degranulated mast cells, was inhibited by the histamine/serotonin antagonists cyproheptadine and methysergide, but was unaffected by the thrombin-specific inhibitor, Hirulog. These findings suggest that through its interaction with EPR-1, Factor Xa may function as a mediator of acute inflammation in vivo. This pathway may amplify both coagulation and inflammatory cascades, thus contributing to the pathogenesis of tissue injury in vivo.

Amino Acid Sequence↗